Biederer T, Südhof T C
Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
J Biol Chem. 2000 Dec 22;275(51):39803-6. doi: 10.1074/jbc.C000656200.
Mint1 (X11/human Lin-10) and Mint2 are neuronal adaptor proteins that bind to Munc18-1 (n/rb-sec1), a protein essential for synaptic vesicle exocytosis. Mint1 has previously been characterized in a complex with CASK, another adaptor protein that in turn interacts with neurexins. Neurexins are neuron-specific cell surface proteins that act as receptors for the excitatory neurotoxin alpha-latrotoxin. Hence, one possible function for Mint1 is to mediate the recruitment of Munc18 to neurexins. In agreement with this hypothesis, we now show that the cytoplasmic tail of neurexins captures Munc18 via a multiprotein complex that involves Mint1. Furthermore, we demonstrate that both Mint1 and Mint2 can directly bind to neurexins in a PDZ domain-mediated interaction. Various Mint and/or CASK-containing complexes can be assembled on neurexins, and we demonstrate that Mint1 can bind to Munc18 and CASK simultaneously. Our data support a model whereby one of the functions of Mints is to localize the vesicle fusion protein Munc18 to those sites at the plasma membrane that are defined by neurexins, presumably in the vicinity of points of exocytosis.
Mint1（X11/人Lin-10）和Mint2是神经元衔接蛋白，它们与Munc18-1（n/rb-sec1）结合，Munc18-1是突触小泡胞吐作用所必需的一种蛋白质。Mint1先前已被鉴定为与CASK形成复合物，CASK是另一种衔接蛋白，它又与神经连接蛋白相互作用。神经连接蛋白是神经元特异性细胞表面蛋白，作为兴奋性神经毒素α- Latrotoxin的受体。因此，Mint1的一种可能功能是介导Munc18向神经连接蛋白的募集。与这一假设一致，我们现在表明神经连接蛋白的胞质尾部通过一个涉及Mint1的多蛋白复合物捕获Munc18。此外，我们证明Mint1和Mint2都可以通过PDZ结构域介导的相互作用直接与神经连接蛋白结合。各种含有Mint和/或CASK的复合物可以在神经连接蛋白上组装，并且我们证明Mint1可以同时结合Munc18和CASK。我们的数据支持一种模型，即Mints的功能之一是将囊泡融合蛋白Munc18定位到质膜上由神经连接蛋白定义的那些位点，大概是在胞吐作用点附近。
